Development of murine leukemia virus-based self-activating vectors that efficiently delete the selectable drug resistance gene during reverse transcription

Expression of the selectable drug resistance gene in retroviral vectors use d for gene therapy can lead to a decreased expression of the gene of intere st and may induce a host immune response, resulting in a decreased efficien cy of gene therapy. In this study, we demonstrate that high-frequency delet ion of direct repeats, an inherent property of reverse transcriptases, can be used to efficiently excise the drug resistance gene during reverse trans cription. One retroviral vector containing a direct repeat deleted the neom ycin resistance expression cassette during a single replication cycle at >9 9% efficiency.